文献类型：期刊文献

英文题名：Decreased Lincomycin B Content by Regulating Osmotic Pressure in Fermentation of Streptomyces lincolnensis

作者：Li, Shengkai[1];Zhang, Liwen[1];Gao, Shuhong[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2023

卷号：28

期号：5

起止页码：874

外文期刊名：BIOTECHNOLOGY AND BIOPROCESS ENGINEERING

收录：;EI(收录号：20233514655367);WOS:【SCI-EXPANDED(收录号:WOS:001191858100001)】；

基金：We thank State Key Laboratory of Bioreactor Engineering and East China University of Science and Technology for the funding and support. This work was supported by National Key Research and Development Program of China (2020YFA0907800) and National Science Foundation of China for Young Scientists (No. 21506056).

语种：英文

外文关键词：Streptomyces lincolnensis; lincomycin; osmotic pressure; sulfur metabolite; transcriptome analysis

摘要：Lincomycin, a clinically important antibiotic against Gram-positive bacteria, is a sulfur-containing metabolite produced by Streptomyces lincolnensis. The main problem in the fermentation is the high content of lincomycin B, which is a by-product of insufficient methylation by S-adenosylmethionine (SAM) dependent methyltransferase. In this study, the content of lincomycin B was decreased from 4.04% to 0.75% and from 8.20% to 5.78% by the addition of NaCl as an osmotic regulator in flask and 15 L bioreactor fermentation, respectively. By analysis of the sulfur-containing metabolites (cysteine, homocysteine, SAM, and ergothioneine) and high-throughput RNA sequencing, the mechanism of osmotic regulation on lincomycin fermentation was studied. The results showed that the synthesis of methyl donor (SAM) and sulfur donor of lincomycin (ergothioneine and mycothiol) were increased at the metabolite level and transcription level under osmotic stimulation; the transcription of genes involved in sulfur assimilation (tauA, ssuA1B1C1) and lincomycin biosynthesis were also up-regulated significantly. This study provides a cost-effective method to reduce lincomycin B and increase the production of lincomycin A. The mechanisms of osmotic pressure regulation on lincomycin fermentation was also elucidated, which may provide more genetically modified targets for overproduction of lincomycin and other sulfur containing secondary metabolites.